A heterocyclic compound constitutes a basic framework of a natural product and an organic phosphorus compound has a pharmacologic activity and a physiological activity. The organic phosphorus compound is largely related with biological phenomenon, many synthesis methods thereof have been attempted to be developed and studied depending on new physiological functions thereof, and in particular, chemical reactivity and physiological relation between carbon in an organic compound and phosphorus in an organic phosphorus compound having a similar structure to the organic compound have received attention.
In particular, a phosphaisocoumarin derivative which is one of a phosphorus heterocyclic compound has a similar activity to a coumarin derivative used as a precursor of perfume, seasoning, and other chemicals. That is, the phosphaisocoumarin derivative may be used as an important precursor preparing medical supplies. A phosphorus 2-pyrone derivative is used for synthesis of various medical supplies including a HIV protease inhibitor, and the like.
Therefore, many researches of developing the synthesis method of the phosphaisocoumarin derivative and the phosphorus 2-pyrone derivative have been conducted (J. Org. Chem. 2006, 71, 8489; Org. Lett. 2013, 15, 26; J. Am. Chem. Soc. 2003, 125, 15006).
A preparation method of the phosphaisocoumarin derivative and the phosphorus 2-pyrone derivative with a high yield by annulation between a phosphinic derivative and various alkynes in the presence of a rhodium (Rh) catalyst or a ruthenium (Ru) catalyst has not been reported yet.
Meanwhile, an isoquinolin-1-one derivative is a significantly important compound showing physiological activities such as an anti-cancer function, function on a toxic cell, function on cardiovascular system, an anti-tumor function, an antibacterial function, inhibition of human thymidylate, inhibition of PARP activity, and maximal blood pressure reduction.
As the existing synthesis method of a phosphaisoquinoline-1-one compound, a synthesis method using o-(1-alkynyl)phenylphosphonamide monoester in the presence of a palladium catalyst is known (J. Org. Chem. 2006, 71, 8489.); however, with the synthesis method, phosphaisoquinoline-1-one having a substitutent introduced at a position No. 4 of a product by an intramolecular annulation may not be synthesized. Recently, a synthesis method of novel phosphaisoquinoline-1-one and a derivative thereof by an olefin reaction with alkyne, and a subsequent annulation reaction through an activation reaction of a carbon-hydrogen bond using a phosphonyl group as a directing group has not been recently reported, and thus, a novel synthesis method of various phosphaisoquinoline-1-one compounds using the same is required to be developed.